Reconstruction of craniofacial defects caused by fracture, trauma or degeneration is one of the major clinical challenges in the Unites States and around the world. The existing treatments have limitations and lack clinical predictability, necessitating the development of new strategies to heal, repair and regenerate the craniofacial bone tissues. The ability to regenerate new bone for craniofacial use is a significant clinical need. One approach to regenerate the tissues of interest is the seeding of autologous stem cells into a biomaterial or scaffold. These biomaterials or scaffolds support and provide cues for the cells, allowing them to grow, differentiate and secrete new extracellular matrix. It is necessary to develop new biodegradable materials, which provide an appropriate microenvironment for cell-matrix interactions that can mimic the important multi-functionality of the biological environment. This proposal focuses on development of a new approach for regenerating natural bone tissues, with emphasis on developing injectable hybrid microparticles (MPs) providing osteoconductivity, osteoinductivity and structural integrity into MPs. This will be achieved by following three specific research aims, as described below: 1. To fabricate and characterize hybrid MPs. 2. To optimize the in vitro release kinetics of growth factors. 3. To test and evaluate hybrid MPs for enhancement of osteogenesis in vitro using bone marrow stromal cells. Public Health Relevance: The relevance of this research to public health exists in the development of novel injectable hybrid microparticles that can be applied for regeneration of lost or damaged bone tissues.